Breast cancer in African-American women occurs at an earlier age than in Caucasian women and is more likely to have aggressive features associated with poorer prognosis, regardless of age at diagnosis. The mechanisms underlying these differences are as yet unknown. Although factors related to socioeconomic status (SES) are likely to play a role in racial differences in stage at diagnosis and disease-free survival, SES factors are unlikely to fully explain the earlier age at diagnosis or the more aggressive nature of breast cancer in African-American women. Most recognized risk factors for breast cancer involve reproductive or hormonal characteristics. Importantly, there are notable differences between African-Americans and Caucasians in distribution of polymorphisms in genes that govern steroid biosynthesis and metabolism, in endogenous hormone profiles, and in menstrual and childbearing histories. These risk factor differences could impact breast cancer in African-American and Caucasian women, although the potential role of SES factors cannot be discounted. To our knowledge, there have been no studies specifically designed and with adequate power to address these questions. Building upon a funded case-control study of bio-behavioral risk factors for breast cancer in African-American women, we propose to investigate determinants of early age at onset and high grade, ER negative disease among African-Americans and Caucasians and to evaluate the proportion of disparities in aggressive disease that can be accounted for by differential distribution of genetic and hormonally-related risk factors in both racial groups. We intend to enroll 1200 Caucasian cases and 1200 controls and to enroll an additional 800 African-American women. We will over-enroll women under age 50 so that we will have equal proportions of younger and older women in both racial groups. Combined with data from the ongoing study, the proposed study will include 1200 African-American women with breast cancer and 1200 controls and an equal number of Caucasians. We hypothesize that factors associated with higher exposures to circulating estrogens, as well as the timing of those exposures, including early age at menarche, early and multiple pregnancies, energy balance and body size, as well as polymorphisms that result in higher active hormone levels will be associated with early age at diagnosis and high-grade, ER negative breast cancer, and that these factors will be more prevalent among African-American than Caucasian women. We will also examine the role of socio-economic factors, including screening behaviors and access to care, in the higher prevalence of high-grade, ER- tumors among African-American women. Results from this study will provide much-needed answers as to why African-American women are more likely than Caucasians to be diagnosed with more aggressive disease at an earlier age.